Bioinformatics-based and multiscale convolutional neural network screening of herbal medicines for improving the prognosis of liver cancer: a novel approach.

Background: Liver cancer is one of the major diseases threatening human life and health, and this study aims to explore new methods for treating liver cancer. Methods: A deep learning model for the efficacy of clinical herbal medicines for liver cancer was constructed based on NDCNN, combined with the natural evolutionary rules of a genetic algorithm to obtain the herbal compound for liver cancer treatment. We obtained differential genes between liver cancer tissues and normal tissues from the analysis of TCGA database, screened the active ingredients and corresponding targets of the herbal compound using the TCMSP database, mapped the intersection to obtain the potential targets of the herbal compound for liver cancer treatment in the Venny platform, constructed a PPI network, and conducted GO analysis and KEGG analysis on the targets of the herbal compound for liver cancer treatment. Finally, the key active ingredients and important targets were molecularly docked. Results: The accuracy of the NDCNN training set was 0.92, and the accuracy of the test set was 0.84. After combining with the genetic algorithm for 1,000 iterations, a set of Chinese herbal compound prescriptions was finally the output. A total of 86 targets of the herbal compound for liver cancer were obtained, mainly five core targets of IL-6, ESR1, JUN, IL1ß, and MMP9. Among them, quercetin, kaempferol, and stigmasterol may be the key active ingredients in hepatocellular carcinoma, and the herbal compound may be participating in an inflammatory response and the immune regulation process by mediating the IL-17 signaling pathway, the TNF signaling pathway, and so on. The anticancer effects of the herbal compound may be mediated by the IL-17 signaling pathway, the TNF signaling pathway, and other signaling pathways involved in inflammatory response and immune regulation. Molecular docking showed that the three core target proteins produced stable binding to the two main active ingredients. Conclusion: The screening of effective herbal compounds for the clinical treatment of liver cancer based on NDCNN and genetic algorithms is a feasible approach and will provide ideas for the development of herbal medicines for the treatment of liver cancer and other cancers.

Sorafenib Plus Hepatic Arterial Infusion Chemotherapy in Advanced Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

This meta-analysis aimed to determine whether sorafenib combined with hepatic arterial infusion chemotherapy is beneficial for advanced hepatocellular carcinoma. We searched PubMed, Cochrane Library, and Embase to identify comparative studies evaluating sorafenib plus hepatic arterial infusion chemotherapy versus sorafenib for advanced hepatocellular carcinoma. Overall survival, progression-free survival, objective response rate, rate of progressive disease, and adverse events were evaluated. This meta-analysis included 5 randomized controlled trials (690 patients). Pooled estimates showed that compared with sorafenib, sorafenib plus hepatic arterial infusion chemotherapy was associated with higher overall survival (hazard ratio = 0.52, 95% CI: 0.28-0.95, P = .03), progressionfree survival (hazard ratio = 0.57, 95% CI: 0.33-0.98, P = .04), objective response rate (risk ratio = 3.84, 95% CI: 1.23-12.05, P = .02), as well as higher rates of neutropenia (risk ratio = 7.90, 95% CI: 3.0-20.78, P < .0001) and thrombocytopenia (risk ratio = 2.73, 95% CI: 1.70- 4.36, P < .0001), but had no significant influence for rate of progressive disease (risk ratio = 0.76, 95% CI: 0.43-1.37, P = .37). Sorafenib plus hepatic arterial infusion chemotherapy improved overall survival, progression-free survival, and objective response rate, but it had no effect on the rate of progressive disease. Combination therapy has a survival benefit for advanced hepatocellular carcinoma patients, and adverse events can be accepted. However, more large-scale randomized controlled trials are needed for further investigation.

Nanoparticle Delivery of Active Traditional Chinese Medicine Ingredients: A New Strategy for the Treatment of Liver Cancer.

The precise treatment of liver cancer is receiving much research attention. Surgery, chemoradiotherapy, and other methods remain the mainstream of this treatment, but many chemotherapeutic drugs used to treat advanced liver cancer cause adverse reactions and have unstable efficiencies. Active ingredients used in traditional Chinese medicine (TCM) have been examined widely in anti-cancer research due to their advantages of multi-pathway targeting and rich pharmacological effects. However, these active components have poor water solubility, bioavailability, and targeting efficiency. Nanomedicine has been applied to improve the efficacy of TCM ingredients in the treatment of liver cancer. Nanoparticles (NPs) show great potential in this context due to their excellent bioavailability, high controlled agent release efficiency, and clear targeting. This paper reviews the application of NPs loaded with active TCM ingredients in the treatment of liver cancer, with the aim of facilitating new vector development and improving the precision treatment of liver cancer.

Polysaccharide-modified liposomes and their application in cancer research.

Nanodrug delivery systems have been widely used in cancer treatment. Among these, liposomal drug carriers have gained considerable attention due to their biocompatibility, biodegradability, and low toxicity. However, conventional liposomes have several shortcomings, such as poor stability, rapid clearance, aggregation, fusion, degradation, hydrolysis, and oxidation of phospholipids. Polysaccharides are natural polymers of biological origin that exhibit structural stability, excellent biocompatibility and biodegradability, flexibility, non-immunogenicity, low toxicity, and targetability. Therefore, they represent a promising class of polymers for the modification of the surface properties of liposomes to overcome their shortcomings. In addition, polysaccharides can be readily combined with other materials to develop new composite materials. Hence, they represent the optimal choice for liposomal modification to improve pharmacokinetics and clinical utility. Polysaccharide-coated liposomes exhibit better stability, drug release kinetics, and cellular uptake than conventional liposomes. The oncologic application of polysaccharide-coated liposomes has become a research hotspot. We summarize the preparation, physicochemical properties, and antineoplastic effects of polysaccharide-coated liposomes to facilitate antitumor drug development.

Anti-Programmed Cell Death (PD)-1 Immunotherapy for Malignant Tumor: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis evaluated anti-programmed cell death (PD)-1 immunotherapy (nivolumab or pembrolizumab) for overall efficacy, safety, and effective dose relative to standard chemotherapy or other conventional drugs in the treatment of malignant tumors. We searched the following databases, PubMed, Medline, Embase, Cochrane, Wangfang Data, Weipu, and China National Knowledge Infrastructure, and the reference lists of the selected articles for randomized controlled trials (RCTs) of anti-PD-1 therapies in humans. The outcome measures were overall survival, treatment response, and adverse events. Only four randomized controlled trials met our inclusion criteria. Three of these evaluated responses to nivolumab, whereas one tested pembrolizumab. The result of our analysis suggested that nivolumab may improve the overall response rate in treating melanoma relative to chemotherapy and has few associated adverse events. Similarly, in metastatic melanoma patients, nivolumab had a significant advantage over dacarbazine in terms of 1-year survival, progression-free survival, and objective response rate. Regarding dose levels of nivolumab for patients with metastatic renal cell carcinoma, the outcomes in response to 2 and 10 mg/kg were similar, but both had significant advantages over 0.3 mg/kg. In addition, pembrolizumab showed similar outcomes in response to 2- and 10-mg/kg treatment. Anti-PD-1 immunotherapy appears to be safe and effective for patients with melanoma or metastatic renal cell carcinoma. Our meta-analysis is limited, but additional clinical trials are warranted to verify this preliminary evidence of positive outcomes and before anti-PD-1 therapy can be recommended for routine clinical use.

The Chinese herb-derived Sparstolonin B suppresses HIV-1 transcription.

BACKGROUND: The Chines herb derived Sparstolonin B, (SsnB), is a recently identified natural compound that selectively blocks TLR2- and TLR4-mediated inflammatory signaling. But it is unknown whether this compound has any effect on HIV infection. FINDINGS: We found that SsnB treatment blocked HIV-1 transcription via a novel mechanism that requires the TAR region. Treatment of human T cell lines or peripheral blood mononuclear cells with SsnB at 1 µM significantly inhibited HIV production. Lastly, SsnB was able to inhibit HIV in synergy with AZT. CONCLUSIONS: These data suggest that SsnB is a novel natural compound that inhibits HIV-1 transcription and may be a new drug in the treatment of HIV infection.

Effect of fluid shear stress on portal vein remodeling in a rat model of portal hypertension.

Aims. To explore the effects and mechanisms of fluid shear stress on portal vein remodeling in a rat model of portal hypertension. Methods. Subcutaneous injections of CCl4 were given to establish a rat model of liver cirrhosis and portal hypertension. Biomechanical technology was adopted to determine the dynamic changes of haemodynamic indices and fluid shear stress. Nitric oxide (NO), synthase (NOS), and endothelin-1 (ET-1) of the portal vein blood were measured. Changes in geometric structure and ultrastructure of the portal vein were observed using optical and electron microscopy. Results. After the CC14 injections, rat haemodynamics were notably altered. From week 4 onwards, PVP, PVF, and PVR gradually and significantly increased (P < 0.05 versus baseline). The fluid shear stress declined from week 4 onwards (P < 0.01 versus control group). NO, NOS, and ET-1 increased after repeated CCI4 injections. Hematoxylin and eosin staining showed thickened portal vein walls, with increased inside and outside diameters. Electron microscopy revealed different degrees of endothelial cell degeneration, destruction of basement membrane integrity, proliferating, and hypertrophic smooth muscle cells. Conclusions. Fluid shear stress not only influenced the biomechanical environment of the portal vein but also participated in vascular remodeling.

Combined immunotherapy with dendritic cells and cytokine-induced killer cells for malignant tumors: a systematic review and meta-analysis.

PURPOSE: A new strategy of adoptive and passive immunotherapy involves combining dendritic cells (DCs) with a subset of natural killer T lymphocytes termed cytokine-induced killer (CIK) cells. The objective of this systematic review and meta-analysis was to evaluate the safety and efficacy of DC-CIK therapy vs. placebo, no intervention, conventional treatments, or other complementary and alternative medicines for malignant tumors. METHOD: We searched PubMed, Medline, Embase, Cochrane, Wangfang, Weipu, CNKI databases and reference lists of articles. We selected randomized controlled trials of DC-CIK therapy vs. placebo, no intervention, conventional treatments, or other complementary and alternative medicines in patients with all types and stages of malignant tumor. Primary outcome measures were overall survival and treatment response. Secondary outcome measures were health-related quality of life (HRQoL) assessment, progression free survival (PFS), and adverse events. RESULTS: Six trials met our inclusion criteria. There was evidence that chemotherapy+DC-CIK increased the 2-year (RR 2.88, 95% CI 1.38 to 5.99, P=0.005) and 3-year (RR 11.67, 95% CI 2.28 to 59.69, P=0.003) survival rates and progression free survival (RR 0.64, 95% CI 0.34 to 0.94, P<0.0001) in patients with non-small cell lung cancer compared to those treated with chemotherapy alone. DC-CIK therapy appears to be well-tolerated by cancer patients and to improve post-treatment patient health related quality of life. CONCLUSION: DC-CIK immunotherapy is a safe and effective treatment for patients with malignant tumors. Further clinical trials to provide supportive evidence for the routine use of DC-CIK therapy in clinical practice are warranted.